Regulation of blood flow and volume exchange across the microcirculation

Abstract

Oxygen delivery to cells is the basic prerequisite of life. Within the human body, an ingenious oxygen delivery system, comprising steps of convection and diffusion from the upper airways via the lungs and the cardiovascular system to the microvascular area, bridges the gap between oxygen in the outside airspace and the interstitial space around the cells. However, the complexity of this evolutionary development makes us prone to pathophysiological problems. While those problems related to respiration and macrohemodynamics have already been successfully addressed by modern medicine, the pathophysiology of the microcirculation is still often a closed book in daily practice. Nevertheless, here as well, profound physiological understanding is the only key to rational therapeutic decisions. The prime guarantor of tissue oxygenation is tissue blood flow. Therefore, on the premise of intact macrohemodynamics, the microcirculation has three major responsibilities: 1) providing access for oxygenated blood to the tissues and appropriate return of volume; 2) maintaining global tissue flood flow, even in the face of changes in central blood pressure; and 3) linking local blood flow to local metabolic needs. It is an intriguing concept of nature to do this mainly by local regulatory mechanisms, impacting primarily on flow resistance, be this via endothelial or direct smooth muscle actions. The final goal of microvascular blood flow per unit of time is to ensure the needed exchange of substances between tissue and blood compartments. The two principle means of accomplishing this are diffusion and filtration. While simple diffusion is the quantitatively most important form of capillary exchange activity for the respiratory gases, water flux across the blood-brain barrier is facilitated via preformed specialized channels, the aquaporines. Beyond that, the vascular barrier is practically nowhere completely tight for water, with paracellular filtration giving rise to generally low but permanent fluid flux outwards into the interstitial space at the microvascular high pressure segment. At the more leaky venular aspect, both filtration and diffusion allow for bidirectional passage of water, nutrients, and waste products. We are just beginning to appreciate that a major factor for maintaining tissue fluid homeostasis appears to be the integrity of the endothelial glycocalyx.

Optical probe pressure effects on cutaneous blood flow

“…Together they lead to a sequence of vasoconstrictions and vasodilation which form fluctuating regime of vasomotion. Physiologically these mechanisms are intended to ensure metabolic requirements of the tissue and interrelated with its metabolic state [1].…”

Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall

“…Endothelial monolayer is critical for normal vascular function. Lesions of endothelium manifested as endothelial dysfunction are linked to various cardiovascular diseases through pathological changes in microcirculation, atherosclerosis of major arteries, and left heart remodeling . Endothelial glycocalyx covers the monolayer and plays important role in maintenance of endothelial integrity .…”

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

“…ECs line all the vasculatures and create a barrier between surrounding tissues and vascular space. They play vital roles in maintaining the viability and functionality of all the organs by regulating tissue homeostasis as well as by allowing the exchange of oxygen, nutrients, and waste products . Depending on the vessel type and physiological need, vasculature in different parts of the body acquires organ‐specific phenotypes and adaptations .…”

“…They play vital roles in maintaining the viability and functionality of all the organs by regulating tissue homeostasis as well as by allowing the exchange of oxygen, nutrients, and waste products. [9] Depending on the vessel type and physiological need, vasculature in different parts of the body acquires organ-specific phenotypes and adaptations. [10,11] For instance, the human brain has highly specialized blood-brain barriers composed of the tightly linked ECs that allow only specific molecules such as nutrients and oxygen to pass through.…”